Submissions for variant NM_003107.3(SOX4):c.499_500insCGG (p.His166_Gly167insAla)

dbSNP: rs542004893

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV001837328	SCV002097870	uncertain significance	Coffin-Siris syndrome 10	2021-02-09	criteria provided, single submitter	clinical testing	The inherited c.499_500insCGG (p.His166_Gly167insAla) variant identified in the SOX4 gene is the in-frame insertion of a single Alanine between amino acids 166-167/475. While this specific variant is absent from gnomAD(v3.1) suggesting it is not a common benign variant in the populations represented in that database, there are other in-frame insertions and deletions present in this region. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.His166 and p.Gly167 residues are not within a mapped domain of SOX4 and are C-terminal to the HMG domain in which pathogenic variants to date have been identified [PMID:30661772]. Given the lack of compelling evidence for its pathogenicity, the inherited c.499_500insCGG (p.His166_Gly167insAla) variant identified in the SOX4 gene is reported as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV004546673	SCV005041843	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	SOX4: PM2, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV004546673	SCV005188814	uncertain significance	not provided		criteria provided, single submitter	not provided